57 research outputs found
Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l
Transitions of cardio-metabolic risk factors in the Americas between 1980 and 2014
Describing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014
Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits
Psychological
and social factors are known to influence blood pressure (BP) and risk
of hypertension and associated cardiovascular diseases. To identify
novel BP loci, we carried out genome-wide association meta-analyses of
systolic, diastolic, pulse, and mean arterial BP, taking into account
the interaction effects of genetic variants with three psychosocial
factors: depressive symptoms, anxiety symptoms, and social support.
Analyses were performed using a two-stage design in a sample of up to
128,894 adults from five ancestry groups. In the combined meta-analyses
of stages 1 and 2, we identified 59 loci (p value < 5e−8), including
nine novel BP loci. The novel associations were observed mostly with
pulse pressure, with fewer observed with mean arterial pressure. Five
novel loci were identified in African ancestry, and all but one showed
patterns of interaction with at least one psychosocial factor.
Functional annotation of the novel loci supports a major role for genes
implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL).
These findings underscore the importance of considering psychological
and social factors in gene discovery for BP, especially in non-European
populations
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